Ascorbate is the only endogenous antioxidant in plasma that can completely protect the lipoproteins from detectable peroxidative damage induced by aqueous peroxyl radicals and the oxidants released from activated PMNs. In contrast to aqueous oxidants, lipid-soluble peroxyl radicals unsparingly induce detectable peroxidative damage to plasma lipids. However, under these conditions, too, ascorbate appears to belong to the first line of antioxidant defense. Our findings strongly suggest that pathologically relevant lipid hydroperoxide formation consequent to acute or chronic leukocyte activation can be prevented by ascorbate supplementation, provided no free metal catalysts are present. Ascorbate should prove very helpful in the treatment and prevention of diseases and degenerative processes caused by oxidative stress.